The Interaction of Drugs with Placebos in the Control of Pain and Anxiety

THE INTERACTION OF DRUGS WITH PLACEBOS IN THE CONTROL OF PAIN AND ANXIETY ALBERT J. DINNERSTEIN, Ph.D., MILTON LOWENTHAL, M.D., and BERNARD BLITZ, Ph.D.* Placebos are pharmacologically inert materials which are administered to patients, or experimental subjects, along with expressed or implied suggestions that they will produce some, usually therapeutic, effect. Despite their pharmacological inertness, placebos are moderately effective in the relief of pain and anxiety. For example, the administration of an inert material with the suggestion that it is analgesic is roughly 50 per cent as effective as morphine in controlling postsurgical pain [1]. Placebos can, moreover, affect almost any of the physiological states which are controlled by the central or autonomic nervous systems [2]. The placebo effects are based on the patient's comprehension of, and emotional response to, the apparent drug administration. This comprehension and emotional response, and their physiological consequence, depend in great part on the instructions or suggestions given to the person receiving the capsule or injection of pharmacologically inert material. The placebo effects thus result from the patient's knowledge that he has been treated plus his conception ofthe nature ofthe treatment. Active drugs could be, but seldom are, administered in a concealed form. Moreover, drugs are almost always given with expressed or implied suggestions concerning some expected effect. The administration of an active drug thus includes the same variables as are involved in the administration of a placebo. For this reason, active drugs always act, in part, as placebos. The observed effect of drug administration is thus a combination ofthe pharmacological effects and the placebo effects. * Department of Physical Medicine and Rehabilitation, New York Medical College-Center for Chronic Disease, Welfare Island, New York 10017. This paper grew out of an ongoing research program concerning pain, begun in 1961, and supported by grants from the Health Research Council ofthe City ofNew York and the Vocational Rehabilitation Administration. ??3 In the not-so-distant past, almost all medicines prescribed by physicians were pharmacologically inert by modern standards [3]. Any value produced by these inert medications was achieved by the placebo effect. The effective physician was one who could, intuitively, devise effective placebos. Recent decades have produced many truly effective drugs, such as hormones and antibiotics. In treating hypothyroidism or a bacterial infection , modern drugs are so powerful and specific in comparison to the placebo that the physician can afford to ignore the placebo effects. Once he has correctly diagnosed the problem as a bacterial infection, for example , he can rely on the appropriate antibiotic to correct the disorder. His skill, or lack ofit, in devising effective placebos is irrelevant. Because some drugs are highly effective and specific against some disorders , independent of the placebo effect, most physicians and scientists depreciate the placebo effects. The placebo effects are viewed as a nuisance which complicate research in pharmacology. One tries to "remove" them, as it were, by the double-blind study. When dealing with highly specific disorders, and with powerful and specific treatments, this approach is adequate. In attempting to control pain or anxiety, however, the above approach is seriously misleading. It misleads scientists in their attempts to devise and evaluate analgesic and tranquilizing drugs. It leads physicians to provide patients with less than optimum treatment. In the control ofpain and anxiety, the power ofdrugs is not dramatically greater than the power ofplacebos. More important is the fact that the pharmacological effects and placebo effects interact with each other. To control pain or anxiety, it is necessary to understand the nature of these interactions. The detailed nature ofthe interactions is, undoubtedly, extremely complex. Many recent studies, however, provide data which suggest a relatively simple hypothesis concerning the general form ofthis interaction. The present hypothesis is as follows: As drugs are normally employed in laboratory studies, clinical research, or clinical practice involving pain or anxiety, they have no predictable effect on a given person except as modifiers of the placebo effects. Rather than producing direct and unambiguous pharmacological effects on a subject's pain or anxiety, drugs act primarily as amplifiers or inhibitors ofthe placebo effects. As stated, this hypothesis may seem shocking and extreme. It leads, 104 AlbertJ. Dinnerstein et al. · Drugs with...